The MUTYH gene provides instructions for creating the MYH glycosylase enzyme, which plays a part in the body’s DNA repair system. This enzyme helps safeguard cells from errors that can arise during normal biological processes. Understanding the MUTYH gene’s role offers insight into how the body maintains its genetic health.
The Role of the MYH Gene
The function of the MYH glycosylase enzyme, encoded by the MUTYH gene, is to correct errors that occur when DNA is copied during cell division. This enzyme is involved in base excision repair, addressing specific DNA damage. It acts as a proofreader that scans the genetic code for a “typo.”
This error arises when guanine, a DNA building block, is altered by oxygen, causing it to incorrectly pair with adenine instead of cytosine. The MYH glycosylase identifies and removes this mispaired adenine, preventing the incorrect pairing from becoming a permanent mutation in subsequent DNA replications. This repair mechanism prevents the buildup of genetic errors that can lead to cellular dysfunction and contribute to tumor formation.
MUTYH-Associated Polyposis
MUTYH-associated polyposis (MAP) is a genetic condition caused by mutations in both copies of the MUTYH gene. Individuals with MAP develop multiple non-cancerous growths, called polyps, predominantly within the colon and rectum. These polyps are frequently adenomas, a type of growth that can become cancerous over time if not managed.
The number of polyps in individuals with MAP can vary significantly, ranging from fewer than 20 to hundreds, often fewer than 100. While these polyps are not cancerous themselves, their development signifies an underlying genetic inability to correct specific DNA errors. This impairment allows mutations to accumulate in other genes, setting the stage for potential cell overgrowth and tumor formation.
Inheritance and Genetic Risk
MUTYH-associated polyposis (MAP) follows an autosomal recessive inheritance pattern, meaning an individual must inherit a mutated copy of the MUTYH gene from both parents to develop the condition. Parents who each carry one mutated MUTYH gene are asymptomatic and do not have MAP themselves; they are considered carriers. Despite not being affected, carriers can pass the mutated gene to their offspring.
If both parents are carriers of a MUTYH gene mutation, their child has a 25% chance of inheriting two mutated copies and developing MAP. There is also a 50% chance that the child will inherit only one mutated gene, becoming a carrier like their parents, and a 25% chance of inheriting no mutated MUTYH genes. Clarifying the genetic status of family members, especially siblings, is important given these inheritance probabilities.
Associated Health Conditions
Individuals diagnosed with MUTYH-associated polyposis (MAP) face an increased lifetime risk of developing colorectal cancer. If polyps are not regularly monitored and removed, the lifetime risk of colorectal cancer for individuals with MAP can be as high as 80% to 90%. The median age for colorectal cancer diagnosis in MAP patients is around 48 years, which is earlier than in the general population.
Beyond colorectal cancer, individuals with MAP also have an elevated risk for developing other cancers. These can include cancers of the duodenum (the first part of the small intestine), with an estimated lifetime risk of approximately 4-5%. There is also evidence of an increased risk for cancers of the ovary, bladder, thyroid, and skin, although these risks are generally lower than for colorectal and duodenal cancers.
Screening and Management
Regular medical surveillance is a standard approach for individuals diagnosed with MUTYH-associated polyposis (MAP) to manage their health risks. Colonoscopies are recommended to begin between the ages of 25 and 30, or earlier based on family history, and should be repeated every one to two years. This frequent screening allows for the detection and removal of polyps before they develop into cancer.
In addition to colonoscopies, upper endoscopies are advised starting between ages 30 and 35, with follow-up frequency depending on the presence and characteristics of polyps found in the stomach and small intestine. Annual physical examinations, thyroid ultrasounds, and skin examinations by a dermatologist may also be considered to monitor for other associated conditions. If the polyp burden becomes too substantial to manage endoscopically, surgical removal of part or all of the colon may be considered.